Routine Vaccination During Pregnancy Among People Living With HIV in the United States

Key Points Question What is the prevalence of routine vaccination among pregnant people living with HIV? Findings In this cohort study of 310 pregnancies among 278 people living with HIV, less than one-third of participants received recommended vaccines in pregnancy: influenza and tetanus, diphtheria, and pertussis. Lower numerical rates of vaccination were observed among multiparous participants and those with perinatally acquired HIV, but the differences did not reach statistical significance. Meaning Given the importance of antenatal vaccination for maternal-child health, the data in this study suggest that pregnant people living with HIV have urgent need for clinical and public health interventions to improve vaccine receipt.


Introduction
Vaccinations are a critical component of routine prenatal care.5][6] Additionally, after 27 weeks' gestation there is fetal benefit with maternal Tdap vaccination, regardless of the recency of prior maternal Tdap vaccination. 2The antenatal Tdap vaccine acts as a protective bridge to the neonate's first dose of the pertussis vaccine at 2 months of life. 6[13][14][15][16][17] Despite extensive and conclusive data on the safety and efficacy of influenza and Tdap vaccines during pregnancy, vaccination in the United States is not universal. 18A nationwide survey of pregnant people conducted between 2019 and 2020 found only 69.2% of pregnant persons reported receiving an influenza vaccination and 56.6% received Tdap.Of this cohort, only 40.3% received both recommended vaccines during pregnancy. 19Retrospective data from an academic medical center in Chicago found higher, but still suboptimal, rates of vaccine uptake in pregnancy, at 70% for influenza and 87% for Tdap. 20Data on COVID-19 vaccination also suggest low receipt in pregnancy; as of July 2021, only 21.8% of pregnant people identified in the CDC vaccine safety database received 1 or more doses of a COVID-19 vaccine during pregnancy. 21,22ccination recommendations for pregnant people living with HIV (PLHIV) mirror those for pregnant people without HIV, with some augmentation (ie, consideration of hepatitis A, hepatitis B, pneumococcal, and meningococcal vaccination, if indicated) due to their immunocompromised status.However, there are few studies on antenatal vaccination for PLHIV.One study from Atlanta assessed vaccination in pregnancy and found that PLHIV were less likely to be vaccinated against either influenza (4.8% vs 10.3%) or the influenza/Tdap combination (39.7% vs 43.3%) compared with peers without HIV. 23Data on other vaccinations among PLHIV are limited but suggest receipt of other vaccines, such as the human papillomavirus (HPV) vaccine, which is recommended to be administered post partum, is similarly low. 24Influenza vaccination rates for the general population of people living with HIV is also suboptimal, with data from a large health system in California from 2013 to 2018 revealing influenza vaccination uptake at 65% to 69% for PLHIV. 25Given the paucity of data on the topic of routine vaccination in PLHIV, our objective was to estimate the prevalence of and identify factors associated with receiving influenza and/or Tdap vaccinations among pregnant PLHIV participating in a large multisite prospective cohort in the United States.

Methods
The Surveillance Monitoring for ART Toxicities (SMARTT) study, conducted by the Pediatric HIV/AIDS Cohort Study (PHACS) network, has been enrolling pregnant PLHIV at 22 US sites since 2007.The SMARTT study is designed to evaluate the safety of antiretroviral medications taken during pregnancy by PLHIV by evaluating pregnancy outcomes and the health of their children, who are living with perinatal HIV exposure but uninfected.Between December 1, 2017, and July 31, 2019, SMARTT PLHIV who were either pregnant or had an enrolled child younger than 5 years of age were invited to participate in the Women's Health Study (WHS), a nested substudy within SMARTT that examined the health of pregnant and nonpregnant PLHIV.The WHS consisted of expanded data collection on pregnancies and maternal health.While new data collection in the WHS took place between 2017 and 2019, the design of the study allowed for earlier medical record abstraction on all pregnancies of PLHIV enrolled in SMARTT.The institutional review board at each site reviewed and

Statistical Analysis
For each vaccine outcome, the proportions of pregnancies with vaccination receipt and exact 95% CIs under a binomial distribution were estimated.Distributions of the demographic and clinical characteristics were summarized with proportions for categorical variables and means for continuous variables.Characteristics of eligible pregnancies are reported overall and for each of the 3 vaccination outcomes.
Univariable and multivariable log-binomial regression models were fit for each of the vaccine outcomes with generalized estimating equations (GEEs) to account for correlation between multiple pregnancies per participant.An exchangeable correlation structure was assumed for univariable models.For multivariable models, modified Poisson regression was used with an independent correlation structure, a simpler structure, to assure model convergence.Three types of multivariable
Finally, in evaluating receipt of both influenza and Tdap vaccines, pregnancies of multiparous PLHIV had an aRR less than 1 relative to pregnancies of nulliparous PLHIV for both vaccines, but the

Discussion
This study is among few of which we are aware to describe the prevalence and correlates of Tdap and influenza vaccination in pregnancy for PLHIV.In this cohort, receipt of Tdap and influenza vaccines in pregnancy was low, with fewer than one-third receiving either vaccination and fewer than one-quarter receiving both vaccines, based on medical records.The relative risk of receiving Tdap or both vaccines was also lower in pregnancies of PLHIV who acquired HIV perinatally than among those acquiring HIV later in life.Additionally, pregnancies of multiparous PLHIV had lower relative risk of receiving the influenza vaccine in pregnancy compared with nulliparous PLHIV, whereas pregnancies of older PLHIV had a greater relative risk of receiving both vaccinations.There were also temporal changes in vaccine receipt seen with higher rates in the latter part of the cohort timeline.
Our results demonstrate low receipt of routine vaccinations in a cohort of pregnant PLHIV.
Vaccine uptake in the general population of pregnant people is below public health goals, with reports of vaccination from the CDC's nationwide survey from 2019 to 2020 showing that 61.2% of pregnant people reported receiving influenza vaccination, 56.6% received Tdap, and 40.3% received both. 27The Tdap vaccination has been recommended as standard of care for every pregnant individual by the CDC's Advisory Committee on Immunization Practices expanded since 2013. 28Data from a single institution demonstrated a temporal finding in Tdap vaccination rates: vaccination uptake increased over time, with an increase from 47.4% to 86.1% between 2011 and 2015. 20wever, our findings suggest an increase between 2014 and 2015 (15.8%) to 2016 and 2017 (40.6%) but then suggests a potential plateau from 2017 onward, as the 2018 and 2019 uptake was stable at 43.9%.Additionally, in this same study by DiTosto et al, 20 it was hypothesized that the 2013 recommendation for Tdap vaccination in pregnancy may have increased influenza vaccine uptake, as receipt of the influenza vaccine went from 61.2% to 72.0% between 2011 and 2015 in the general pregnant population.A trend toward similar findings was seen in our data, although further work is required.
Like previous studies, we found nulliparity to be associated with higher probability of influenza vaccine receipt, whereas the association of parity with vaccination was less pronounced for Tdap. 20,29This difference may be explained by the perceived difference between the Tdap and influenza vaccines.Tdap is counseled as a vaccine for fetal and neonatal benefit while influenza is counseled as a vaccine to prevent maternal as well as neonatal morbidity and mortality.Individuals who are pregnant for the first time may be more hesitant to take on the personal risk of influenza illness than those who have been through a pregnancy.It is important to note that vaccination in pregnancy is not only important for the maternal-fetal dyad, but a person's decision to decline recommended vaccinations in pregnancy is a predictor for poor childhood vaccine uptake.
In this diverse cohort, the aRRs for receipt of both vaccines were less than 1 among individuals who did not identify as Black (compared with those who were Black), although findings did not achieve statistical significance.This finding contrasts with other studies that observed lower receipt of vaccination during and outside of pregnancy among people identifying as Black. 313][34][35][36] A rigorous, multipronged approach to understand the role of social determinants of health with regard to vaccination and address them through policy change and programmatic intervention is urgently needed. 37 found that people with perinatally acquired HIV had lower rates of vaccination in pregnancy compared with those who acquired HIV later in life.This finding fits with other data comparing clinical outcomes between these 2 groups.[40][41][42] Pregnancy is a period of enhanced health care access and engagement, serving as a critical window of opportunity for preventive health interventions such as vaccination.Additionally, pregnant people are at increased risk of morbidity and mortality from infections such as influenza. 18us, counseling about and receiving antenatal vaccinations are of utmost importance for all pregnant people, especially those with immunocompromising comorbidities like HIV.4][45] Evidence-based interventions to improve vaccine receipt exist in pediatric and adolescent care, where vaccinations are an integral part of routine care.Successful interventions incorporate a multipronged approach in efforts to improve vaccine uptake.Novel interventions, such as reminder text messages to parents, web-based informational sites, and placing prepopulated orders in clinic records to limit health care professional error, have demonstrated improved outcomes. 46,47In the adult population, a randomized clinical trial demonstrated that in a group of predominantly racial and ethnic minority participants, a pneumococcal vaccination video and brochure was associated with increased vaccination rates compared with being shown an informational video alone.This dual information approach was also associated with more

Strengths and Limitations
One strength of our study is that this is the largest assessment of routine vaccination for pregnant PLHIV to date and includes data from a well-characterized, nationally representative cohort.Our diverse population is also a strength, as pregnant people from underrepresented communities are often not included in research.
However, there are limitations to note.Although participants were enrolled prospectively, the data on vaccination receipt do not offer additional insight beyond whether and when the vaccine was administered; data obtained via medical record abstraction do not detail the reasons for lack of vaccination.Such reasons may include inadequate clinician recommendation for vaccination, participant refusal of vaccination, or barriers to health care access that preclude vaccination.
Retrospective data review of medical records may also underestimate vaccination, such as when patients received vaccination in an outside medical system.Despite SMARTT being one of the largest studies of its kind in the United States, our sample size is limited due to the subset of pregnancies with data collection on vaccination, thus restricting power to detect difference by covariates of interest.Additionally, the confidence intervals estimated for the outcomes may be affected by correlation between repeat pregnancies. 51Furthermore, the participants who enrolled in the SMARTT cohort may not represent the HIV community with respect to vaccination, as they may feel more comfort and integration with the health care system and potentially have higher vaccination rates compared with those who chose not to participate in SMARTT.Future work should corroborate these results in larger and ongoing cohorts.

Conclusions
Understanding barriers to and perspectives on routine vaccination for pregnant PLHIV is of vital importance to improve the health outcomes of pregnant people and their infants.Our data demonstrate suboptimal receipt of antenatal vaccines with evidence-based benefit in a cohort of pregnant PLHIV.Clinicians, researchers, and public health systems must identify and evaluate the impact of innovative and impactful strategies, including improved patient-facing messaging, as the current approach is unsuccessful at achieving the clinical and public health goals of widespread antenatal vaccination.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: Nonauthor members of the Pediatric HIV/AIDS Cohort Study (PHACS) appear in Supplement 2.

Disclaimer:
The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or US Department of Health and Human Services.
models were fit: model 1 included only demographic characteristics, model 2 included only clinical characteristics, and model 3 included all demographic and clinical characteristics.The quasilikelihood under the independence model criterion (QIC) statistics were compared across the 3 models to assess model fit. 26Model 3's QIC demonstrated best fit and is presented in the results as the adjusted estimates.All statistical tests were 2-sided and conducted with an α of less than .05.All analyses were performed using SAS software, version 9.4 (SAS Institute).
Routine Vaccination During Pregnancy Among People Living With HIV This report follows the STROBE reporting guidelines for observational studies.The study population for this analysis was derived from participants in the WHS(Figure).The analysis for this study began in October 2021 and was completed in March 2022.Eligibility was restricted to people with available vaccination data in pregnancy and who delivered on or after March 15, 2015, through February 28, 2020.The primary outcome was vaccination receipt during JAMA Network Open.2024;7(5):e249531.doi:10.1001/jamanetworkopen.2024.9531(Reprinted) May 2, 2024 2/14 Downloaded from jamanetwork.comby guest on 05/04/2024 approved the study.Participants provided written informed consent prior to their participation in SMARTT.information or if the mother was co-enrolled in AMP Up and had medical record abstracted data available.

JAMA Network Open | Obstetrics and Gynecology
49,50nt discussion about the vaccine.48However,littlesuchworkhas extended to pregnant PLHIV.Our findings build upon prior published literature that demonstrate that people have suboptimal receipt of recommended vaccines in pregnancy and show that pregnant PLHIV are even less likely to receive these recommended vaccinations relative to historical general population estimates.Individuals in this population may also have not been offered a vaccine.Future studies utilizing self-reporting methods and comparing survey research methods with chart abstractions would be beneficial for better comparing our results with those of other studies.Alternatively, it could be that the lower prevalence of vaccination receipt we observed was due to lack of trust in the health care system, which can influence health care utilization for PLHIV.PLHIV are often from communities that have been systematically disenfranchised, exploited, and marginalized and as a result may face barriers to accessing high-quality health care, or have experienced discrimination or been mistreated in other ways during medical encounters, which could increase skepticism of health care systems.49,50Futureresearch on interventions and innovation in counseling and information dissemination is needed among pregnant PLHIV to better understand the reasons for and circumstances surrounding suboptimal receipt of vaccines during pregnancy.Understanding the perspectives of pregnant people with and without HIV regarding vaccination during pregnancy is crucial and can inform successful clinical and social interventions to improve vaccination during pregnancy.Our team is conducting ongoing qualitative work on this issue, aiming to identify targeted programming and interventions capable of improving routine vaccination in pregnancy.Such work also needs to address how strategies that are developed for well-established vaccinations can be JAMA Network Open.2024;7(5):e249531.doi:10.1001/jamanetworkopen.2024.9531(Reprinted) May 2, 2024 9/14 Downloaded from jamanetwork.comby guest on 05/04/2024 documented physicianrapidly adapted to novel vaccinations, particularly for vulnerable populations.Future work should also consider clinician-and health system-based barriers to receiving recommended vaccinations during pregnancy.